Synaptopodin-2 (SYNPO2)

Synaptopodin-2 (SYNPO2), also known as myopodin, is a cytoskeletal actin-binding and actin-bundling protein, primarily localized in the Z-disc of striated muscle and implicated in the assembly and stabilization of actin filament bundles[2][4]. It regulates cytoskeletal architecture, cell migration, and intracellular signaling between cytoskeleton and nucleus[2]. Functionally, SYNPO2 is involved in autophagosome formation and selective autophagy pathways, and plays major roles in muscle maintenance and repair[4]. In cancer biology, SYNPO2 has been variably characterized as a tumor suppressor or oncogene, depending on the tissue context. Abnormal expression of SYNPO2 is linked to dysregulated cell migration, enhanced metastasis, and altered response to chemotherapy, particularly in prostate, bladder, and breast cancers[3][1]. SYNPO2 expression also modulates tumor immune microenvironment by increasing infiltration of innate immune cells, specifically mast cells, and confers resistance to immune checkpoint inhibitors and certain chemotherapies, while increasing sensitivity to PI3K/AKT pathway-targeted drugs[3].

Other names

Synaptopodin-2SYNPO2MYOPODINGenethonin-2Myopodinsynaptopodin-2 (alternate orthography)genethonin-2 (alternate orthography)myopodin (alternate orthography)Fesslin (in some literature)

Not direct ligandable drug target; however, high SYNPO2 expression correlates with resistance to conventional chemotherapies (paclitaxel, cisplatin, doxorubicin) and increased sensitivity to PI3K/AKT pathway inhibitors in cancer cells[3]. Modulates actin cytoskeleton regulation, cell adhesion/motility, and influences innate immune cell (mast cell) infiltration in the tumor microenvironment[3].