Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia (By similarity). Required for epidermal adhesion (PubMed:15838507). Involved in the development of eyelids and the anterior segment of the eyeballs (PubMed:30802441). Interacts with FREM1. First expressed from 10 dpc in the mesodermal core of the branchial arches, developing lens, otic vesicle and limb apical ectodermal ridge. Later, it is expressed in the vibrissae and vibrissae pad, eyelids ear and pelage follicles and, at low levels, in the epidermis (PubMed:15838507). Also expressed in caudal somites and, in later embryos, in facial, limb and intercostal muscles (PubMed:15838507). In contrast to Frem1, it is not expressed in the developing mammary glands or in the caecum (PubMed:15838507). Restricted to the epithelia in a pattern complementary to that of Frem1 (which is generally expressed in the dermis and mesenchyme) (PubMed:15838507). In the developing kidney, it is expressed At in the mesonephric and metanephric epithelia at 11.5 dpc, with a highest expression at the tips of the developing ureteric buds (PubMed:15838507). At 12.5 and 13.5 dpc, it is still expressed throughout the epithelial components of the kidney, including epithelia fated to form nephrons, which are induced by the ureter tips to differeintiate from the mesenchymal condensations that surround them (PubMed:15838507). Expressed in retinal neuron-containing outer plexiform layer (PubMed:30802441). The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding. Mice display cryptophthalmos, syndactyly and renal defects. Frem2 corresponds to the X-ray irradiated-induced allele 'myelencephalic blebs' (my). Belongs to the FRAS1 family.