TRIM44 as a Multifunctional Regulator in Cancer and Non-Cancer Diseases: From Oncogenic Driver to Immune and Stress Response Modulator

Abstract

Tripartite motif-containing protein 44 (TRIM44), a unique member of the TRIM family that lacks the canonical RING domain, has recently attracted significant attention for its broad oncogenic potential across diverse malignancies. Accumulating evidence indicates that TRIM44 is markedly overexpressed in cancers, including colorectal, gastric, lung, breast, ovarian, and prostate carcinomas, as well as glioblastoma, multiple myeloma, and hepatocellular carcinoma. Mechanistically, TRIM44 drives tumor progression by modulating critical signaling pathways, including PI3K/AKT/mTOR, NF-kappa B, Wnt/beta-catenin, and epithelial-mesenchymal transition (EMT), primarily through stabilizing regulatory proteins or participating in non-coding RNA-mediated networks. In addition to its role in cancer, TRIM44 has been implicated in cardiovascular dysfunction, ischemia-reperfusion injury, diabetic complications, and neuroinflammation, underscoring its biological versatility. This review provides an overview of current evidence regarding the multifaceted roles of TRIM44 in both oncogenic and non-oncogenic diseases. By integrating insights from oncology, cardiology, neurology, and metabolic research, this review offers a unified perspective on TRIM44 as a pivotal molecular hub and an emerging diagnostic and therapeutic target.