LNX1 is a PDZ domain-containing E3 ubiquitin ligase that regulates protein stability and cellular signaling through non-degrading ubiquitination and substrate degradation. Primary function: LNX1 acts as a catalytic E3 ligase and molecular scaffold, ubiquitinating multiple substrates including p53, RhoC, connexin36, and liprin-α1 1234. The protein localizes to neuronal synapses and gap junctions where it mediates protein internalization and synaptic plasticity 3. Mechanism: LNX1 contains a RING catalytic domain and four PDZ domains enabling both direct ubiquitination and scaffolding functions 4. It negatively regulates p53 stability via MDM2-dependent ubiquitination and suppresses RhoC activity through LIS1-mediated regulation 12. Disease relevance: LNX1 shows altered expression and copy number variations in nervous system tumors and gliomas 5. Dysregulation contributes to cancer progression through p53 inactivation in wild-type p53 cancers and suppression of cancer stemness in colorectal carcinoma 16. High LNX1-AS2 expression predicts poor prognosis in lung adenocarcinoma 7. Clinical significance: LNX1 is essential for hippocampal social memory formation via NMDAR complex assembly, and deficiency causes neurodevelopmental social cognitive deficits 8.