RNF122 is an E3 ubiquitin ligase containing a RING finger domain localized to the endoplasmic reticulum and Golgi apparatus 1. It functions as a C3H2C3-type RING finger-containing E3 ubiquitin ligase that mediates proteasome-dependent protein degradation and undergoes self-ubiquitination 2. RNF122 interacts with calcium-modulating cyclophilin ligand (CAML), which stabilizes RNF122 protein 2. A primary physiological role involves suppressing antiviral immunity by targeting RIG-I caspase activation and recruitment domains for Lys-48-linked ubiquitination and proteasomal degradation, thereby inhibiting type I interferon production 3. RNF122 can induce both necrosis and apoptosis in cell-based assays 4. Clinically, RNF122 shows disease relevance across multiple conditions: it is upregulated in glioblastoma where it promotes tumor growth via JAK2/STAT3/c-Myc pathway activation and correlates with poor prognosis 5; it associates with colorectal cancer progression 6; genetic variants show association with attention deficit hyperactivity disorder with evidence of overexpression in affected adults 7; and it mediates immune cell effects on major depressive disorder risk 8. These findings identify RNF122 as a multifunctional ubiquitin ligase with significant roles in cancer progression, innate immunity, and neuropsychiatric disease.