SEDLIN, which is encoded by the spondyloepiphyseal dysplasia late gene is a highly conserved 140 amino acid protein with a.95% identity amongst vertebrate orthologues and a.30% identity to the yeast Trs20p. The crystal structure of mouse Sedlin shows it to have a single domain structure that contains 20 solventaccessible apolar residues. Four of these apolar residues constitute the Desogestrel hydrophobic pocket and the hydrophobic groove, both of which may act as protein-binding sites. Indeed, SEDLIN has been reported to interact with proteins that are not part of the TRAPP complex, but are Etidronate either transcription factors, such as the c-myc promoterbinding protein 1, pituitary homeobox 1 and steroidogenic factor 1, or the intracellular chloride channels, CLIC1 and CLIC2. Interestingly, SEDLIN has been reported to localize to the perinuclear structures, although the reported interactions with the transcription factors MBP1, PITX1 and SF1, would also suggest a role for SEDLIN in the nucleus. Mutations of SEDLIN have been reported in patients with spondyloepiphyseal dysplasia tarda, an X-linked osteochondrodysplasia that is characterised by short stature, a disproportionate short trunk, barrel-shaped chest, narrowing of the intervertebral disc spaces, platyspondyly, a shortened femoral neck, and early onset secondary osteoarthritis which may require hip replacement before the age of 40 years. The forty-four disease-causing SEDL mutations, which had been reported at the commencement of these studies, consisted of 40 that resulted in premature truncations and 4 that were missense mutations. However, the functional consequences of these SEDL mutations at the cellular level remain unidentified and we hypothesised that these may involve a loss of interactions with MBP1, PITX1 and SF1, particularly as PITX1 and MBP1, which is also referred to as enolase1, have been reported to have roles in endochondral ossification and maintenance of adult bone. Moreover, PITX1 expression has been reported to be significantly reduced in osteoarthritic cartilage, and citrullinated enolase1, which is a known rheumatoid arthritis autoantigen, is expressed at high levels in rheumatoid joints.