Cartilage intermediate layer protein (CILP), an extracellular matrix protein, shows abundant expression in cartilagenous tissues. CILP is expressed as two isoforms, CILP and CILP-2, which are differentially expressed by chondrocytes and induced by TGF∫1. This induction is mediated by Smad3 through direct interactions with cis-elements in the CILP promoter region. TGF∫ also induces elevated chondrocyte extracellular inorganic pyrophosphate (PPi), which promotes the deposition of calcium pyrophosphate dihydrate crystals. The CILP isoforms have been implicated in common musculoskeletal disorders, including osteoarthritis, rheumatoid arthritis and lumbar disc disease.