PSMC1 encodes a critical ATPase subunit of the 26S proteasome, which is essential for ATP-dependent degradation of ubiquitinated proteins and maintenance of cellular protein homeostasis 1. As part of the heterohexameric AAA-ATPase ring, PSMC1 functions to unfold ubiquitinated target proteins and translocate them into the proteolytic chamber for degradation 1. The protein localizes to multiple cellular compartments including the nucleus, cytosol, and centrosome, where it interacts with other proteasome components and regulatory proteins like TOPORS 2. Disease-causing variants in PSMC1 result in severe neurological phenotypes, including a recently described autosomal recessive syndrome characterized by developmental delay, intellectual disability, spastic tetraplegia, and hearing loss 1. Functional studies demonstrate that pathogenic PSMC1 variants disrupt ATP binding and hydrolysis domains, leading to proteasome dysfunction 1. Mouse studies reveal that complete loss of Psmc1 is lethal, while heterozygous knockout causes cell cycle defects in embryonic fibroblasts but no apparent neuropathology 3. Interestingly, population-based genetic studies found no association between PSMC1 variants and Parkinson's disease susceptibility, despite the protein's role in protein quality control 4. The emerging understanding of PSMC1 dysfunction contributes to the growing class of neurodevelopmental proteasomopathies.