TMOD2 (tropomodulin 2) is an actin-binding protein that caps the pointed end of actin filaments, thereby regulating actin filament dynamics and cytoskeletal organization 1. In the nervous system, TMOD2 exhibits neuronal-specific expression and plays critical roles in neurite outgrowth, dendritic spine formation, and synaptic morphology, contributing to structural and functional neural plasticity 1. TMOD2 is a major regulator of plasticity in the mesolimbic system, controlling drug-induced synaptic plasticity and the reinforcing properties of cocaine 2. Dysregulation of TMOD2 is implicated in multiple diseases. In Alzheimer's disease, TMOD2 emerged as part of high-performance biomarker panels (AUC = 0.987) for diagnosis and prediction of cognitive decline in cerebrospinal fluid 3. In colorectal adenomas, TMOD2 serves as a gut microbiota-associated biomarker linked to cell adhesion pathways critical for adenoma progression 4. In colorectal cancer, elevated TMOD2 expression correlates with advanced disease stages and poorer survival, with TMOD2 promoting cancer progression through modulation of cytoskeletal dynamics, cell adhesion, and liver metastasis 5. TMOD2 also functions in centrosome regulation through binding with NPM2, with chr15 exposure disrupting this interaction and inducing centrosome amplification 6. Additionally, miR-191-5p acts as a tumor suppressor in prostate cancer by downregulating TMOD2 expression 7. These findings position TMOD2 as a multifunctional regulator with implications across neurodegenerative, psychiatric, and neoplastic diseases.