RNF31. also known as HOIP (HOIL-1-interacting protein), is a critical component of the linear ubiquitin chain assembly complex (LUBAC), which regulates NF-κB signaling by catalyzing the formation of Met1-linked (linear) ubiquitin chains. This post-translational modification is essential for immune response regulation, cell death pathways, and inflammation. RNF31 contains a RING-IBR-RING domain that facilitates its E3 ligase activity, enabling LUBAC to modify substrates like NEMO/IKKγ and RIPK1. thereby modulating NF-κB activation. Antibodies targeting RNF31 are vital tools for studying its expression, localization, and function in both physiological and pathological contexts. They are widely used in techniques such as Western blotting, immunofluorescence, and immunoprecipitation to investigate LUBAC dynamics in diseases like cancer, autoimmune disorders, and chronic inflammation. Dysregulated RNF31 expression has been linked to tumor progression, resistance to apoptosis, and aberrant immune responses. Research using RNF31-specific antibodies has highlighted its role in maintaining cellular homeostasis and its potential as a therapeutic target. However, challenges remain in dissecting its complex interactions within LUBAC and its substrate specificity. These antibodies also aid in exploring pharmacological inhibitors of LUBAC for conditions driven by hyperactive NF-κB signaling. Overall, RNF31 antibodies are indispensable for advancing our understanding of ubiquitin-dependent signaling networks and their implications in human health.