ANKH transports PPi from cytosol to extracellular region

Progressive ankylosis protein homolog (ANKH) is a putative transmembrane pyrophosphate (PPi) transport channel protein found in osteoblasts of various bones. It mediates the transport of cytosolic PPi to the extracellular matrix. Abnormal transport of PPi is implicated in familial calcium pyrophosphate dihydrate deposition (CPPD) disease. There are two forms of CPPD disease: CCAL1 and CCAL2. Defects in ANKH can cause chondrocalcinosis (CCAL2; MIM:118600), a chronic condition in which PPi crystals deposit in the joint fluid, cartilage, and periarticular tissues and there is calcium deposition in articular cartilage (Pendleton et al. 2002, Williams et al. 2002, Williams et al. 2003). Defects in ANKH can also cause craniometaphyseal dysplasia, autosomal dominant (CMDD; MIM:123000), an osteochondrodysplasia characterised by progressive thickening and increased mineral density of craniofacial bones and abnormal modelling of metaphyses in long bones (Nurnberg et al. 2001, Reichenberger et al. 2001).

渐进性骨硬化蛋白同源物（ANKH）是一种假定的跨膜焦磷酸盐（PPi）转运通道蛋白，存在于多种骨骼的成骨细胞中。该蛋白介导细胞质PPi向细胞外基质的转运。PPi转运异常与家族性焦磷酸钙二水合物沉积病（CPPD）相关。CPPD疾病有两种形式：CCAL1和CCAL2。ANKH基因缺陷可导致软骨钙化病（CCAL2；MIM:118600），这是一种慢性病症，表现为PPi晶体沉积于关节液、软骨和关节周围组织，以及关节软骨中的钙沉积（Pendleton等，2002，Williams等，2002，Williams等，2003）。ANKH基因缺陷还可导致颅骨 metaphyseal发育不良（CMDD；MIM:123000），一种以颅面部骨骼渐进性增厚和矿化密度增加，以及长骨 metaphyseal异常塑形为特征的骨软骨发育不良（Nurnberg等，2001，Reichenberger等，2001）。