Tropomyosin alpha-4 chain

Tropomyosin alpha-4 chain (TPM4) is a 248-amino acid protein that binds actin filaments and regulates muscle contraction through calcium-dependent mechanisms in striated muscle and caldesmon-mediated regulation in smooth muscle (UniProt: P67936). In non-muscle cells, it stabilizes cytoskeletal actin filaments and contributes to platelet biogenesis. A documented variant causes Bleeding disorder, platelet-type, 25 (BDPLT25), an autosomal dominant platelet dysfunction disorder.

In Alzheimer's disease, TPM4 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.31; Chaparral AD proteomics). The downregulation was detected in a single subcellular fraction across a TMT-labeled differential proteomic analysis using four subcellular fractions (P2, P3, S2, S3). This reduction may reflect cytoskeletal remodeling or impaired actin dynamics characteristic of neurodegenerative pathology, though the functional consequences in AD remain to be clarified.