RNF112 (ring finger protein 112) is a brain-specific E3 ubiquitin ligase and dynamin-like GTPase with dual catalytic activities that regulate neuronal development and cancer progression. During brain development, RNF112 initiates neuronal differentiation by inducing G0/G1 cell cycle arrest 1. Structurally, RNF112 contains a GTPase domain and RING finger domain; its GTPase activity regulates dendritic spine density through endosomal membrane remodeling 2, while its E3 ligase function mediates K48-linked polyubiquitination of target proteins 3. In the adult brain, RNF112 maintains neural functions and protects tissue from oxidative stress 4. Clinically, RNF112 is significantly downregulated across multiple cancer types—bladder, gastric, and colorectal cancers—correlating with disease progression. RNF112 suppresses bladder cancer proliferation, migration, and lipid synthesis via ubiquitin-mediated c-Myc degradation 3. In gastric cancer, RNF112 directly ubiquitinates FOXM1, suppressing proliferation and invasion 5. In colorectal cancer, KLF4-regulated RNF112 inhibits growth through NAA40 degradation 6. Additionally, RNF112 modulation associates with antidepressant effects, with altered RNF112 expression supporting synaptic and mitochondrial homeostasis in depression models 78. Mutations in RNF112 serve as independent prognostic factors in oral squamous cell carcinoma 9.