LRRC55 (leucine-rich repeat containing 55) functions as an auxiliary protein that modulates large-conductance, voltage and calcium-activated potassium (BK) channels. It produces a marked ~50 mV hyperpolarizing shift in the BK channel's voltage dependence of activation in the absence of calcium, positioning it within a γ family of BK channel auxiliary proteins distinct from classical β-subunits 1. LRRC55 shows tissue-specific expression predominantly in brain 1. In pathological contexts, upregulated LRRC55 promotes BK channel activation, leading to potassium loss and increased intracellular calcium, which triggers apoptosome formation and caspase-3 activation 2. Elevated LRRC55 expression occurs in podocytes from patients with focal segmental glomerulosclerosis, diabetic nephropathy, and membranous nephropathy 2. Genetic variants in LRRC55 (rs717117) associate with reduced anti-TNF drug response in rheumatoid arthritis patients, particularly those who are rheumatoid factor-positive, via mechanisms involving altered IL-6 production 3. Additionally, a common variant near the LRRC55 locus (rs11604583) associates with increased deep vein thrombosis risk 4. Beyond ion channel regulation, a cytoplasmic lncRNA (lncLrrc55-AS) antisense to LRRC55 enhances antiviral innate immune responses by promoting IRF3 phosphorylation 5.