STK38 is a serine/threonine kinase with multifaceted cellular functions spanning signal transduction, DNA damage response, and organellar homeostasis. Canonically, STK38 acts as a negative regulator of MAP3K1/2 signaling by converting phosphorylated MAP3K2 to its inactive form and inhibiting its autophosphorylation 1. Beyond kinase activity, STK38 functions as a UFM1-protein reader, recognizing mono-ufmylated histone H4 at double-strand breaks to promote SUV39H1 recruitment and ATM activation 2. STK38 regulates lysosomal homeostasis by phosphorylating DOK1 to recruit VPS4 for ESCRT disassembly during microlysophagy, a process critical for preventing cellular senescence and aging 3. Additionally, STK38 phosphorylates XPO1 to activate the major nuclear export receptor, regulating subcellular localization of proteins including YAP1 and Beclin1 4. Clinically, STK38 exhibits complex roles in cancer: it suppresses colorectal cancer through the NLRP12/STK38/GSK3β axis inhibiting Wnt/β-catenin signaling 5, while in triple-negative breast cancer, CAPG-171aa disrupts STK38-SMURF1 binding to promote MEKK2 activation and tumor growth 6. STK38 stabilizes GPX4 phosphorylation in hepatocellular carcinoma, conferring ferroptosis resistance 7. Pan-cancer analysis demonstrates STK38 expression correlates with prognosis and immune cell infiltration across multiple malignancies 8.