The BRICHOS domains from proSP-C (D105) and Bri2 (D148) were selected (Fig. 1a and b), since these two proteins are associated with different human diseases, i.e., ILD and familial dementias, respectively, possess different chaperone activity spectra, and have only ∼17% amino acid sequence identities.13,32,36. Here, ITM2B is linked to interstitial lung disease.