SCYL3 (SCY1-like pseudokinase 3) is a conserved pseudokinase that regulates intracellular trafficking and cell migration pathways. Functionally, SCYL3 acts as a component of COPI-mediated Golgi trafficking machinery, working in concert with COPI coat proteins to regulate Golgi morphology and protein glycosylation 1. In migrating cells, SCYL3 localizes to lamellipodia and interacts with ezrin to regulate cell adhesion and migration complexes 2. Mechanistically, SCYL3 functions through protein-protein interactions; notably, it physically binds ROCK2 (Rho kinase 2) and regulates its stability and transactivating activity, promoting actin stress fiber and focal adhesion formation 3. SCYL3 also maintains motor neuron viability through overlapping redundancy with SCYL1, regulating TDP-43 proteostasis to prevent neurodegeneration 4. Clinically, SCYL3 is overexpressed in hepatocellular carcinoma and associated with worse patient survival and metastasis 3. Additionally, genetic variants in SCYL3 are associated with cardioembolic stroke susceptibility in oligodendrocytes 5. SCYL3 also serves as a gene biomarker for distinguishing Zika from Dengue virus infections in computational models 6. Together, these findings establish SCYL3 as a multifunctional regulator with implications for cancer progression, neurodegeneration, and viral disease pathophysiology.