SCYL1 is a pseudokinase that functions as a transcriptional activator and regulator of intracellular membrane trafficking 1. It localizes to multiple cellular compartments including the Golgi apparatus, endoplasmic reticulum-Golgi intermediate compartment, and centrosomes, where it regulates vesicular transport and protein secretion 2. Mechanistically, SCYL1 is phosphorylated by mTORC1 at Ser754, controlling Golgi architecture and extracellular vesicle secretion; dephosphorylation leads to endosomal redistribution and altered secretory function 3. In cancer contexts, SCYL1 promotes malignancy through distinct pathways: it activates mTORC1 signaling to inhibit autophagy and promote gastric cancer metastasis 4, and its overexpression is associated with poor prognosis in breast cancer 1. Loss-of-function SCYL1 mutations cause acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome (CALFAN), characterized by progressive cholestasis and multisystem involvement due to impaired vesicular trafficking and increased endoplasmic reticulum stress 2. SCYL1 also maintains motor neuron viability through overlapping redundancy with SCYL3, regulating TDP-43 proteostasis 5. These findings position SCYL1 as both an oncogenic target and a critical regulator of organ-specific secretory function.