Targeting the xylosyltransferase TMEM5 in glioblastoma to modulate CLOCK and CRY1 expression and restore temozolomide sensitivity via the circadian signaling axis

TMEM5 is associated with circadian-gene expression patterns, temozolomide response, and bioenergetic readouts in GBM models. TMEM5 knockdown was accompanied by altered time-dependent expression profiles of multiple clock genes, reduced OCR/ECAR parameters under the tested conditions, and increased TMZ sensitivity. These findings support TMEM5 as a circadian-associated factor in GBM and provide a rationale for future studies to define whether TMEM5 directly influences circadian regulation and metabolic pathway remodeling in vivo.