4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol is reduced to 4,4-dimethylcholesta-8(9),24-dien-3beta-ol [LBR]

4,4-dimethylcholesta-8(9),14,24-trien-3beta-ol and NADPH + H+ react to form 4,4-dimethylcholesta-8(9),24-dien-3beta-ol and NADP+, catalyzed by LBR in the nuclear envelope. LBR protein spans the inner nuclear envelope, has an aminoterminal region with properties of a laminin receptor and a carboxyterminal domain with sequence similarity to sterol delta14-reductases (Holmer et al. 1998). Studies of material from an individual with HEM/Greenberg skeletal dysplasia indicate that LBR catalyzes the sterol delta14-reductase step of cholesterol biosynthesis in vivo. DNA sequencing revealed homozygosity for a mutant LBR allele encoding a truncated protein in the affected individual, and cells from the individual accumulated cholesta-8,14-dien-3beta-ol in culture. Transfection of wild-type LBR into the cultured cells reversed the accumulation of cholesta-8,14-dien-3beta-ol (Waterham et al. 2003). This observation is surprising because a second gene, TM7SF2, encodes an efficient sterol delta14-reductase that is localized to the endoplasmic reticulum whose expression is up-regulated in response to sterol depletion (Bennati et al. 2006). The physiological roles of LBR and TM7SF2 in vivo remain to be determined.

4,4-二甲基胆甾-8(9),14,24-三烯-3β-醇与NADPH + H+反应生成4,4-二甲基胆甾-8(9),24-二烯-3β-醇和NADP+，此反应由位于核被膜中的LBR催化。LBR蛋白横跨内核被膜，其氨基末端区域具有层粘连蛋白受体的特性，而羧基末端区域则与甾醇δ14-还原酶（Holmer等，1998）具有序列相似性。对一位患有HEM/Greenberg骨骼发育不良的个体的材料进行研究显示，LBR在体内催化胆固醇生物合成中的甾醇δ14-还原酶步骤。DNA测序揭示了受影响个体中LBR突变等位基因的纯合性，编码的蛋白质截短，且个体的细胞在培养中积累了胆甾-8,14-二烯-3β-醇。将野生型LBR转染至培养细胞中可逆转胆甾-8,14-二烯-3β-醇的积累（Waterham等，2003）。这一观察结果令人惊讶，因为第二个基因TM7SF2编码了一种高效的甾醇δ14-还原酶，该酶定位于内质网，其表达在甾醇耗竭时上调（Bennati等，2006）。LBR和TM7SF2在体内的生理作用尚待确定。