Spicule formation in the sea urchin is one of the conspicuous cellular processes occurring in early embryo-genesis, in which stereotyped spicules form through deposition of minerals onto the spicule matrix protein scaffold. This process requires many genes to be functional: the spicule matrix alone needs more than 50 different genes. Until now, however, only a few skeletogenic genes have been known. Recently SM37, a new putative spicule matrix protein gene, was cloned and found to be linked to SM50 (Lee et al., 1999). The structure of the new gene raised the possibility of the presence of a gene family involved in skeletogenesis which consists of SM50, SM37 and LSM34 (a homologue of SM50) (Benson et al., 1987; Livingston et al., 1991). Characteristics of the gene family include: (1) skeletongenic mesenchyme-specific expression, (2) onset of gene expression as early as the mesenchyme blastula, (3) presence of glycine, proline and glutamine-rich repeats in the middle of the proteins. Another feature of the family is the presence of conserved sequence motifs at both the amino-terminal and carboxyl-terminal regions of the proteins – SCYR(A/Y)F and PNPXXXRPRM(L/Y)QE, respectively – which we speculate play a role in protein guidance.