The initial synthesis of UiO-66(Zr) was performed by first mixing Zr6 oxoclusters with acetic acid. Water, ethanol, and benzene-1,4-dicarboxylic acid (BDC) were subsequently introduced in the oxocluster solution. After 2 h at room temperature under stirring, the resulting solid showed a PXRD pattern (see Figure ) in agreement with the theoretical diffraction pattern of UiO-66. Transmission Electron Microscope (TEM) indicated a particle size of 40 nm (±7) (Figure ). This value is close to the particle size (44 nm) calculated from Scherrer equation, indicating that the particles are well-crystalline. The 77K N2 adsorption (Figure ) showed a type I isotherm with extremely high N2 capacity (404 cm 3 /g) and a calculated Brunauer-Emmett-Teller (BET) surface area (1617 (±5) m 2 /g) larger than the BET surface area of defectfree UiO-66(Zr) (1000 m 2 /g). Such a huge expansion in the surface area is indicative of the formation of a large amount of defects. No symmetry-forbidden peak at low angle (under 27) was observed in the PXRD pattern of the sample, suggesting the absence of missing cluster defects that would lead to an ordered structure with reo topology (Figure ). Thus, we hypothesized the presence of missing linkers in our material. Fourier transform infrared spectroscopy (FTIR) demonstrated the absence of uncoordinated carboxylic acid residual groups in the washed materials, in agreement with the presence of linker defects (Figure ). Thermogravimetric analysis (TGA) under oxygen atmosphere evidenced that the 40 nm UiO-66 nanoMOF exhibited a very low ligand-to-metal ratio (linker:Zr6 = 3.96:1, Figure ), in agreement with a high missing linker content. The number of missing ligands in our sample corresponds to one of the most defective UiO-66 reported so far and concomitantly, to the best of our knowledge, the surface area of 40 nm UiO-66 represents the highest value reported compared to the state-of-the-art. The general method we developed to control the particle size is illustrated in Figure . As our first attempt led to highly defective 40 nm UiO-66 while using only 10 mL EtOH with 50 mg of BDC, the reaction media was further diluted stepwise with EtOH (20, 40, 80 mL, respectively) enabling a better dissolution of the BDC ligand. Interestingly, this led to a dramatic reduction of nanoparticle size, as evidenced by the PXRD patterns in Figure . Notably, when the volume of ethanol reached 80 mL, only a broad envelop of the main characteristic diffraction peaks of UiO-66 could be observed due to the considerable loss of longrange order, which is consistent with Scherrer equation. The TEM images (Figure , S7, S8, and Figure ) evidenced the precise control of downsizing down to between 4 nm and 6 nm. Nevertheless, the crystal lattice planes can still be observed by TEM (Figure ), confirming the crystallinity of the nanoparticles. The selected area electron diffraction (SAED) pattern only showed the characteristic rings (no diffraction spots) of the UiO-66 nanoparticles with different crystal orientations (Figure ), further proving the crystallinity of these nanoMOFs, as well as homogeneous size distribution. Further enlargement of Figure (i) clearly shows the pores and crystallinity of a 4.4 nm nanoparticle, in good accordance with the structural model from Figure (ii). From the profile analysis on HRTEM images along (220) and ( ) directions (Figure ), the distances between two adjacent Zr6 oxoclusters are highly homogeneous with an average value of 1.1 nm that is close to the theoretical one (1.2 nm), suggesting that the defects are missing linkers in our HD-US-UiO-66(Zr). To be noted, such a small particle corresponds to only ca. 2 unit-cell dimensions, i.e. 8 unit-cells or 13 octahedral-cages per nanoparticle. This system therefore lies at the frontier between nanocrystals and discrete metal-organic polyhedra. However, to be noted, although Metal-Organic Cages/Polyhedra (MOCs/ MOPs) have intrinsically discrete supramolecular architectures, they often strongly suffer from poor chemical/hydrolytic stabilities and structural collapse upon activation, preventing their applications. According to TGA, all the different as-prepared nanoparticles exhibited very similar linker content, with close to 2 missing linkers per formula (Figure ). This, once combined with nuclear magnetic resonance (NMR) analysis (Figure ) and Energy Dispersive X-ray spectroscopy (EDX) (Figure ), leads to a general formula of Zr6O4(OH)4(BDC)3.9(C2H3O2)0.8(H2O)2.9Cl0.5. Note that the connection of crystal size to defectiveness in our syntheses is the first of its kind and allows for achieving <5 nm MOF nanoparticles with defectiveness up to 4.2 missing linkers per oxocluster, by far exceeding the commonly reported values (Figure ). Nitrogen porosimetry at 77K on the activated highly defective UiO-66 particles (HD-US-UiO-66) evidenced in all cases a high sorption capacity (from 404 cm 3 /g to 260 cm 3 /g, Figure ) associated with a hysteresis. A decrease of N2 adsorption capacity occurred upon downsizing, in line with a progressive increase of the external to internal surface ratio. Pore size distribution analyses (DFT model) indicated overall a preserved pore size (Figure ), which is once again in line with the constant missing linker content. For the sake of comparison, we followed the conventional MIDA, as well as the synthetic parameters of 40 nm UiO-66 and carried out a set of synthetic experiments by reducing the amount of acetic acid. Noteworthy, the preparation of smaller particles, down to 5 nm, denoted as MI-US-UiO-66 (modulator-induced ultrasmall UiO-66), is associated with lower number of defects (2.6 missing linkers per Zr6 oxoclusters) in good accordance with the previous findings where the missing linker defect content strongly depended on the modulator quantity (see SI for details).