LZTS3 (leucine zipper tumor suppressor family member 3) is a tumor suppressor protein with dual roles in synaptic function and cancer regulation. In neuronal contexts, LZTS3 localizes to postsynaptic densities and dendritic spines, where it interacts with Sipa1l3/SPAR3 and likely regulates dendritic spine morphogenesis through modulation of SIPA1L1 levels 1. The protein shows allele-specific expression in brain tissue, particularly in the superior frontal gyrus, suggesting cis-regulatory mechanisms may influence its function in neurological contexts 2. In cancer, LZTS3 functions as a tumor suppressor across multiple malignancies. In colorectal adenocarcinoma, LZTS3 inhibits cell proliferation and migration by targeting the NOTCH signaling pathway and regulating TAGLN expression 3. Similarly, in lung cancer, LZTS3 suppresses tumorigenesis and radioresistance, though its function is regulated by CK1δ and β-TrCP-mediated ubiquitination through conserved degron sequences 4. Thalidomide can upregulate LZTS3 expression to reduce radiation-induced apoptosis and inflammation in oral epithelial cells 5. LZTS3 has been identified as both a protective and risky prognostic biomarker in colorectal cancer depending on the study context 67.