Nonetheless, the production of these pigments, i.e. melanogenesis, can also induce abnormal levels of melanin accumulation, leading to hyperpigmentation disorders, melasma or skin lesions, and ultimately causing health issues and disfigurements, sometimes severe and profoundly affecting the quality of life. In addition, melanoma is closely related to an uncontrolled synthesis of melanins, which promotes the emergence of resistance to almost all traditional anti-cancer therapies. As a consequence, melanoma is the most deadly skin cancer (more than 60% of the deaths related to skin cancers), while its incidence rate is low (1% of the skin cancers). This multiresistance could be bypassed by the administration of inhibitors as adjuvants in immuno-, chemo-or radiotherapy for sensitizing melanoma, thereby improving the prognosis of the disease. Overall, the inhibition of hsTYR is a well-established strategy for lowering or suppressing melanogenesis in vivo, and numerous inhibitors have been developed in the past decade for therapeutic and/or dermocosmetic purposes (Figure ). However, the production of properly matured hsTYR in high amounts is a challenge, due to its multiple specific N-glycosylations unavailable in simple organisms such as E. coli for recombinant production, mostly jeopardizing large-scale inhibitor screenings. Hence, most studies only relied on in vitro inhibition assays using the cheap and readily-available mushroom tyrosinase from Agaricus bisporus (abTYR), despite a low homology between these two enzymes (22% identity) and very distinct interaction patterns. As a consequence, even the most widely used compound in human-directed dermocosmetic applications, i.e. kojic acid (KA), is a hundredfold less active against hsTYR than abTYR (Ki = 350 µM vs. 4.3 µM), resulting in the use of high concentrations, thereby promoting associated adverse effects, such as dermatitis or erythema, as well as carcinogenicity. Generally, such activity gaps were observed for almost all TYR reference inhibitors, including hydroquinone, arbutin, benzoic acid and several simple resorcinol derivatives. Therefore, a development process involving an appropriate array of tests performed using human models appears as a requirement for producing melanogenesis suppressors that could act efficiently and safely in a human context.