SCYL2 (SCY1-like pseudokinase 2) is a conserved pseudokinase that regulates intracellular protein trafficking and neuronal function. As a component of clathrin-coated vesicles, SCYL2 regulates clathrin-dependent endocytosis at the plasma membrane, trans-Golgi network, and endosomal system 1. The protein suppresses excitotoxicity in the developing brain by regulating excitatory receptor expression at synapses, essential for normal neuronal signaling and brain development 1. SCYL2 also functions in viral restriction by recruiting protein phosphatase 2A (PP2A) to dephosphorylate the HIV-1 protein Vpu, thereby enhancing BST2-mediated viral particle restriction in response to interferon signaling 2. In the WNT pathway, SCYL2 interacts with EPRS to modulate WNT/GSK-3β/β-catenin signaling 3. Biallelic loss-of-function mutations in SCYL2 cause arthrogryposis multiplex congenita-4 (AMC4), a severe neurodevelopmental disorder characterized by microcephaly, corpus callosum agenesis, epilepsy, and global developmental delay 14. SCYL2 mutations have also been identified as candidate genes for intellectual disability in consanguineous populations 5. SCYL2 family members, including SCYL1 and SCYL3, show overlapping roles in maintaining motor neuron viability, with combined deficiencies producing motor neuron degeneration and TDP-43 pathology 6.