Abstract

Lysosomal associated membrane protein family member 5 (LAMP5), a recently identified member of the LAMP family, has been associated with poor prognosis in multiple cancer types; however, its precise oncogenic mechanisms remain unclear. This study systematically investigated the oncogenic and immunological functions of LAMP5 using multiple datasets. LAMP5 expression was significantly dysregulated in various cancers, highlighting its potential as a diagnostic and prognostic biomarker. GSVA indicated that LAMP5 expression is likely associated with enhanced cell proliferation and tumor invasive potential; it may also be correlated with alterations in anti-tumor immune responses. Immune infiltration analyses using Multi-database analyses revealed that high LAMP5 expression was associated with increased infiltration of immune cells including natural killer T cells and tumor-associated fibroblasts, accompanied by upregulation of immune checkpoint molecules and chemokines. Validation using various immunotherapy cohorts showed that elevated LAMP5 expression may be linked to reduced immunotherapy efficacy. A focused investigation in bladder cancer revealed that LAMP5 facilitates proliferation via regulation of the FBXW11/p27 axis. These findings identify LAMP5 as a multifunctional oncoprotein with both prognostic and therapeutic relevance in bladder cancer. This study provides insights into the molecular mechanisms by which LAMP5 promotes bladder cancer progression and offers potential targets for therapeutic intervention and clinical management. Graphical abstract