NEURL4 is a multifunctional E3 ubiquitin ligase with primary roles in centrosomal homeostasis and mitochondrial regulation. As a daughter centriole protein, NEURL4 localizes to procentrioles through its Neuralized homology repeat and promotes CP110 ubiquitination and proteasomal degradation 1. By counteracting CP110 accumulation, NEURL4 maintains normal centriolar architecture and prevents formation of ectopic microtubule organizing centers (MTOCs) 12. NEURL4 functions within a regulatory complex with the HECT E3 ligase HERC2, where HERC2-dependent ubiquitination of NEURL4 contributes to centrosome integrity 2. Beyond centrosomal functions, NEURL4 exhibits ADP-ribosyltransferase (ART) activity as the primary mitochondrial ART enzyme 3. NEURL4-mediated ADP-ribosylation of mitochondrial proteins, particularly mtLIG3, regulates mitochondrial DNA integrity through base excision repair 3. NEURL4 also participates in p53 pathway regulation by modulating p53 oligomerization state within the NEURL4-HERC2 complex, affecting MDM2-p53 feedback regulation 4. Clinically, de novo NEURL4 mutations have been identified in idiopathic male infertility with differential expression in impaired spermatogenesis 5, suggesting reproductive significance. NEURL4 associates with Parkinson's disease-linked LRRK2, modulating Notch signaling through endosomal trafficking and influencing dopaminergic neuron function 6.