DLGAP5 (DLG associated protein 5) is a mitotic spindle-associated protein with critical roles in cell cycle regulation and disease pathogenesis. Primary Function: DLGAP5 regulates spindle assembly and chromosome 14 through interaction with TACC3 1, and functions as a cell cycle regulator that promotes progression through G1/S phases 2. Mechanism: DLGAP5 operates through multiple protein-stabilization pathways: it stabilizes E2F1 transcription factor via USP11-mediated deubiquitination 3, stabilizes MYC protein through USP11 interaction creating positive feedback loops 4, and upregulates PLK1 to promote cell proliferation 5. In prostate cancer, TFAP4 transcriptionally activates DLGAP5, which subsequently activates JAK2/STAT3 signaling 6. Disease Relevance: Biallelic DLGAP5 variants cause spindle assembly defects leading to recurrent early embryonic arrest and female infertility 1. DLGAP5 overexpression drives malignancy across multiple cancers including lung adenocarcinoma, bladder cancer, prostate cancer, and glioblastoma, promoting proliferation, migration, invasion, and chemoresistance 54378. Clinical Significance: High DLGAP5 expression correlates with poor prognosis, advanced tumor stage, and resistance to immunotherapy and chemotherapy 2. DLGAP5 represents a promising diagnostic biomarker and therapeutic target; inhibitors including AT9283 and AAPK-25 show promise in suppressing tumor growth 57.