Melanocyte

Melanocytes sit on the basement membrane among basal keratinocytes (≈1 melanocyte per 4–10 basal cells; ≈1000–2000/mm² depending on site) but form no desmosomes with them. In routine sections they appear as clear cells. Long dendrites extend between keratinocytes of the basal and spinous layers; each melanocyte supplies melanin to about 36 keratinocytes, forming an epidermal melanin unit.

Melanin is made inside melanosomes, lysosome-related organelles that mature through stages I–IV. The copper-dependent enzyme tyrosinase oxidises tyrosine to DOPA and then dopaquinone, which is converted either to brown-black eumelanin or, when cysteine is incorporated, to red-yellow pheomelanin. Mature melanosomes travel along the dendrites and are transferred to keratinocytes (by phagocytosis of dendrite tips), where they cluster over the nucleus as a supranuclear cap that absorbs UV radiation and scavenges free radicals.

Pigmentation is regulated by α-MSH (and ACTH) acting on the melanocortin-1 receptor (MC1R); UV-induced DNA damage activates p53 in keratinocytes, which upregulates POMC/α-MSH — the basis of tanning. Loss-of-function MC1R variants cause red hair, freckling and a pheomelanin-rich, UV-sensitive phenotype. Melanocytes also reside in hair bulbs, the uveal tract and retinal pigment epithelium (the latter neuroectodermal), the inner ear (stria vascularis) and leptomeninges.