A missense variant in <i>Kallikrein-15</i> (KLK15 p. Gly226Asp), segregated with disease in two families and genetic burden analyses of 197 sporadic hEDS patients revealed enrichment of variants within the <i>Kallikrein</i> gene family. Here, KLK15 is linked to Ehlers-Danlos syndrome, hypermobility type.