Most patients with HAE have reduced plasma C1-INH activity (5%–30% of normal) due to reduced C1-INH protein (type 1) or a dysfunctional C1-INH variant (type 2) (Table 1, right column) (Kaplan and Joseph, 2010; Schmaier, 2019; Bova et al., 2020; Busse and Christiansen, 2020; Lumry and Settipane, 2020; Farkas et al., 2022b). Here, SERPING1 is linked to hereditary angioedema.