Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L) (CLPTM1L)

Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L), also known as Cisplatin resistance-related protein 9 (CRR9), is a multi-pass transmembrane protein primarily localized to the endoplasmic reticulum and plasma membrane [1, 2]. It is encoded by a gene in the 5p15.33 chromosomal region, a locus strongly associated with susceptibility to various cancers, including lung, pancreatic, and bladder cancers [3, 4]. CLPTM1L functions as an anti-apoptotic factor that protects cells from genotoxic stress, particularly DNA damage induced by platinum-based chemotherapeutic agents like cisplatin [2, 5]. It achieves this by modulating the PI3K/Akt signaling pathway and interacting with components of the DNA damage response machinery [5, 6]. In many malignancies, CLPTM1L is overexpressed, promoting tumor cell survival, migration, and resistance to treatment [4, 7]. While no small-molecule inhibitors are currently approved, CLPTM1L mRNA is a target for experimental RNA interference (siRNA) and antisense oligonucleotide (ASO) therapies designed to sensitize resistant tumors to chemotherapy [2, 8]. Research indicates that its downregulation can significantly increase the efficacy of DNA-damaging agents in lung and ovarian cancer models [5, 7]. Additionally, the rs401681 polymorphism within the CLPTM1L gene is one of the most frequently cited genetic markers for lung cancer risk in genome-wide association studies [3].

Other names

CRR9Cisplatin resistance-related protein 9Cleft lip and palate transmembrane protein 1-like

Inhibition of CLPTM1L expression or function to sensitize cells to chemotherapy-induced apoptosis.