Lamin B receptor (LBR)

Lamin B receptor (LBR) is an integral multi-spanning membrane protein of the inner nuclear membrane, characterized by eight transmembrane domains and a large N-terminal region containing a tudor domain and serine-arginine-rich motifs[1][2][3][4]. LBR’s bifunctional nature enables it to act as both an enzyme (sterol C14-reductase, catalyzing a necessary step in cholesterol biosynthesis) and as a structural protein that anchors heterochromatin to the nuclear periphery, helping to establish nuclear architecture and regulate gene expression[1][4][5]. Mutations in LBR cause distinct diseases depending on mutation type—including the benign Pelger–Huët anomaly and the lethal Greenberg skeletal dysplasia—correlating with loss of enzymatic activity and/or protein stability[3][4]. LBR dysfunction or reduced expression is also implicated in cellular senescence and potentially in cancer progression, due to its role in chromatin structure and gene silencing[5]. The essential functions of LBR in cholesterol synthesis and nuclear organization, as well as its involvement in human disease, define its relevance as a biomedical target.

Other names

Delta(14)-sterol reductase LBRDelta-14-SRC14SRDHCR14BTDRD183-beta-hydroxysterol Delta(14)-reductaseC-14 sterol reductaseIntegral nuclear envelope inner membrane proteinLMN2RSterol C14-reductasetudor domain containing 18PHAPHASK

In theory, inhibitors would block sterol C14-reductase activity, impacting cholesterol biosynthesis. Modulators could alter chromatin structure by impacting LBR’s tethering function.