UBAP1 (ubiquitin associated protein 1) is a core component of the ESCRT-I complex that regulates endosomal sorting and protein degradation. Functionally, UBAP1 binds ubiquitinated cargo proteins and directs their sorting into multivesicular bodies (MVBs) for lysosomal degradation 1. The protein recognizes ubiquitinated substrates through its UEV domain-containing complex partners and mediates microautophagy of protein aggregates, including tau and STING 23. UBAP1 also plays a homeostatic role in terminating innate immune signaling by promoting STING degradation at endosomes, thereby regulating type I interferon responses 3. Additionally, UBAP1 localizes to damaged lysosomes to coordinate lysosomal repair and maintains proper mTORC1 signaling localization 4. Disease relevance is significant: loss-of-function mutations in UBAP1 cause spastic paraplegia 80 (SPG80), a rare hereditary spastic paraplegia characterized by juvenile-onset progressive lower limb spasticity 51. SPG80 mutations impair UBAP1 recruitment to endosome membranes, causing accumulation of ubiquitinated proteins, aberrant endosome clustering, and neurodegeneration 1. Notably, a SPG80 UBAP1 mutant enhances STING-dependent interferon responses in immune cells, suggesting immune dysregulation contributes to disease pathology 3. Rapamycin treatment shows promise in restoring lysosomal homeostasis and attenuating disease progression in UBAP1-deficiency models 4.