RNF114 (ring finger protein 114) is an E3 ubiquitin-protein ligase that regulates diverse cellular processes through substrate-specific ubiquitination. The protein promotes K48-linked ubiquitination leading to proteasomal degradation of various targets 1. RNF114 functions as a key regulator of DNA damage response by targeting PARP1 for degradation in a PARylation-dependent manner, with its recruitment to DNA lesions being essential for PARP1 removal 2. The enzyme recognizes ubiquitinated ADP-ribose through its tandem zinc fingers and ubiquitin interacting motif domains, subsequently elongating substrates with K11-linked ubiquitin chains 3. In metabolic regulation, RNF114 ubiquitinates phosphoglycerate dehydrogenase at Lys310 and Lys330, promoting its degradation and controlling serine synthesis 4. The protein also regulates cytoskeletal dynamics in T cells by binding to filamentous actin and causing its downregulation, which affects cellular traction forces and cytotoxicity 5. In cancer contexts, RNF114 promotes hepatocellular carcinoma progression by facilitating GSK3β ubiquitination and degradation, activating Wnt/β-catenin signaling 6. Additionally, RNF114 contributes to colorectal cancer metastasis through the degradation of junction plakoglobin 1. These diverse functions establish RNF114 as a critical regulator of cellular homeostasis, DNA repair, metabolism, and cancer progression 7.