Reptiles exhibit a spectacular diversity of skin colors generated by interactions among black melanophores, red and yellow xanthophores, as well as iridophores producing structural colors. Here, we use the corn snake to investigate the generative mechanisms of skin colors beyond the zebrafish model. We perform sequencing and annotation of a nearly chromosome-quality genome of the corn snake, followed by mapping-by-sequencing and identification of a mutation in the lysosomal trafficking regulator gene ( LYST ) in the lavender variant with strongly affected coloration. Further analyses indicate that color-producing organelles of all chromatophores are substantially impacted in the LYST mutant, indicating that not only melanosomes, but also xanthosomes and iridosomes, are all lysosome-related organelles.