RC3H2 encodes a multifunctional protein that serves as both an RNA-binding post-transcriptional regulator and E3 ubiquitin ligase. The protein binds to constitutive decay elements (CDEs) in target mRNAs, promoting their deadenylation and degradation independently of miRNAs 1. Structurally, RC3H2 contains ROQ and HEPN domains that undergo conformational changes to accommodate both stem-loop and double-stranded RNA binding 1. As an E3 ubiquitin ligase, RC3H2 pairs with multiple E2 enzymes to generate polyubiquitin chains and is involved in ubiquitinating MAP3K5/ASK1, thereby regulating stress responses and ROS-induced cell death 21. The protein plays critical roles in immune regulation, controlling inflammation by suppressing TNF expression in macrophages and preventing spontaneous T follicular helper cell differentiation. RC3H2 has been implicated in various disease contexts, including associations with cognitive function 3, cardiovascular disease risk 4, suicide attempt behavior 5, and osteoporosis regulation through ceRNA networks 6. Additionally, RC3H2 expression changes with aging in periodontal ligament stem cells, affecting their regenerative capacity 7, and responds to NB-UVB treatment in atopic dermatitis patients 8.