The serine/threonine-protein kinase 19 (STK19) was originally reported to phosphorylate α-casein at serine/threonine residues and histones at serine residues. Recently, it has been implicated in a transcription-related DNA damage response. However, the role of STK19 in cancer initiation and development is poorly appreciated. Importantly, STK19 harbors significant somatic hotspot mutations in 5% of melanoma and 10% of skin basal cell carcinoma respectively, and is listed among the top melanoma driver genes. This strong genetic evidence implies an important, but uncharacterized role of STK19 in melanocyte malignant transformation and melanoma progression. STK19 is an NRAS-activating kinase with frequent gain-of-function mutations. Evidence was shown, that blockade of STK19 represents an effective therapeutic strategy for NRAS mutant melanomas.[1]