Melanins are synthesized within melanocytes in a specialized organelle, the melanosome, and are deposited on filaments within it. We investigate the organelle's structure and biogenesis and protein functions within it. Using immunologic, microscopic, and molecular methods, we study how proteins are sorted to melanosomes. Cell lines adapted to culture and capable of synthesizing and packaging melanin in vitro, some in a hormonally regulated fashion, aid us in this work. Over 150 coat-color mutations can be studied in the laboratory mouse. Interestingly, at least 13 of these may affect both the melanosomal structure and lysosomal functions. We explore the relationship between melanosomes and the lysosomal/prelysosomal compartment. These studies will help us understand genetic disorders that alter skin and eye pigmentation in humans, including some fascinating multisystem disorders that affect multiple organelles, of which the melanosome is but one. Additionally, evidence reveals that some melanosomal proteins may also be expressed on the surface of malignant melanocytes; understanding how to modulate the protein trafficking may have implications for melanoma detection and treatment.