OLFM1 (olfactomedin 1) is a secreted glycoprotein with multifaceted roles in nervous system development and function. Structurally, OLFM1 forms disulfide-linked tetramers with a distinctive V-shaped architecture stabilized by calcium, with C-terminal β-propeller domains that contain calcium binding sites 1. Functionally, OLFM1 promotes axonal growth by binding to the Nogo A receptor (NgR1) complex and inhibiting its interaction with coreceptors p75NTR and LINGO-1, thereby preventing NgR1-mediated growth cone collapse 2. It also modulates Wnt signaling to regulate retinal axon extension and eye development 3. Beyond the nervous system, OLFM1 regulates epithelial-mesenchymal transition (EMT) by promoting cell invasion during heart valve formation, cooperating with TGFβ signaling 4. OLFM1 deficiency impairs female fertility primarily through defective olfaction, affecting the accessory olfactory bulb's response to pheromones and subsequently disrupting reproductive hormone signaling 5. Clinically, reduced serum OLFM1 correlates with Alzheimer's disease severity, cognitive decline, and hippocampal/angular gyrus atrophy, particularly in APOE ε4 carriers, positioning it as a potential peripheral biomarker 6. Additionally, decreased plasma OLFM1 associates with poor survival outcomes in systemic sclerosis-associated pulmonary hypertension 7.