PROTACs are heterobifunctional molecules that selectively degrade a protein of interest (POI). The mechanism of action (MoA) of PROTACs proceeds via the formation of a ternary complex with a POI and an E3 ligase, which then induces a proximity-induced ubiquitination of the POI on a surface lysine, and subsequent degradation by the ubiquitin-proteasome pathway. A hallmark of these protein degraders is the catalytic nature of degradation, which enables recycling of the PROTAC after dissociation from the ternary complex. This unique MoA results in a longer lasting pharmacological effect relative to conventional non-covalent inhibition, enabling lower dosages for their application in vivo. A further advantage of PROTACs over conventional inhibitor strategies is the need to engage the POI ultimately for degradation rather than a modulation of protein function by stoichiometric interaction with a small molecule. At present, one major limitation of the application of PROTACs is their lack of cell selectivity and variable levels of cell permeability, which is reflected in their sub-optimal pharmacokinetic properties. Incorporating a cell-targeting module into PROTAC designs has the potential to deliver the PROTAC cargo to the desirable cell type(s), and subsequently, minimise off-target toxicity (Figure ). An emerging platform for the cell-selective delivery of PROTACs is their conjugation to an antibody (Ab). Ab-drug conjugates (ADCs) combine the ability to selectively deliver a molecular payload, such as a PROTAC, to specific cell types, thereby bypassing the need for extensive optimization of the cell uptake properties to the PROTAC scaffold (Figure ). Whilst Ab-PROTACs have been developed for the cell-selective degradation of BRD4 and ER, the impact of how the linkage chemistry (i.e., cleavable vs. non-cleavable), drug accumulation into a target cell type and the diversity of POI which can be targeted by Ab conjugation is still in its infancy. Herein, we expand the scope of Ab-PROTAC conjugates by demonstrating the cell-selective and targeted degradation of serine/threonine-protein kinase 2 (RIPK2) in HER+ cell lines (Figure ).