LRFN4 is a transmembrane protein containing leucine-rich repeats and fibronectin type III domains that functions primarily in neuronal development and synaptic organization. In the nervous system, LRFN4 promotes neurite outgrowth in hippocampal neurons and regulates synaptic assembly by redistributing the postsynaptic density protein PSD95 to the cell periphery through its C-terminal PDZ-binding domain 1. The protein is expressed predominantly in brain tissue and exhibits developmental stage-specific expression patterns 1. Beyond its neuronal functions, LRFN4 demonstrates significant roles in cancer biology and immune cell regulation. In monocytes and macrophages, LRFN4 expression increases during differentiation and promotes cell migration through actin cytoskeleton reorganization, forming signaling complexes with 14-3-3s and NCK1 proteins to activate Rac1-mediated cellular elongation 23. In cancer contexts, LRFN4 shows dysregulated expression across multiple tumor types and serves as a prognostic biomarker, with high expression correlating with better survival outcomes in colorectal cancer patients 4 and association with immune infiltration patterns in gastric cancer 5. The protein's N-glycosylation by ALG3 is critical for its oncogenic functions in bladder cancer metastasis 6, highlighting its therapeutic potential as both a biomarker and treatment target.