RNF144A and RNF144B: Important molecules for health

RNF144 family proteins, including RNF144A and RNF144B, members of the RING-between-RING domain-containing ubiquitin E3 ligase family, serve as critical regulators of protein ubiquitination. Despite increasing research attention in recent years, particularly regarding their distinct functional roles in pathophysiological processes, a comprehensive synthesis of existing findings remains absent. To address this knowledge gap, we conducted a systematic literature search in PubMed using the following query terms: "RNF144," "RNF144A," "RNF144B," "PIR2," "IBRDC2," and "P53RFP." This review systematically examines current evidence regarding the molecular mechanisms and pathophysiological significance of RNF144A/B across various disease systems. Through critical analysis of structural characteristics, substrate interactions, and signaling pathways, we aim to clarify their dual roles in cellular homeostasis and disease pathogenesis. This synthesis not only consolidates current understanding but also identifies key knowledge gaps requiring further investigation, particularly regarding isoform-specific functions and therapeutic targeting potential.