WES has been the mainstay of highly successful disease‐gene discovery studies over the past decade, resulting in the identification of several genes responsible for metabolic bone disorders (e.g. WNT1 mutations as causes of osteoporosis and OI 19; SFRP4 mutations in Pyle's disease 54; AP2σ mutations in FHH type 3 33; PLS3 mutations in X‐linked osteoporosis 18; BMP1 mutations causing increased BMD and recurrent fractures 87; and CYP3A4 mutations in vitamin D‐dependent rickets, type 3 88). This evidence concerns the gene PLS3 and osteoporosis.