To better address the engagement of IGFBP3 as circulating in blood with TMEM219 expressed in target cells, we first demonstrated, through analysis of immunofluorescence distribution at the single-cell level, a colocalization between serum IGFBP3 and TMEM219 in beta cells cultured in vitro with T1D serum, which was not evident in those cultured with non-diabetic serum or with FBS (Fig. 3u and Supplementary Fig. 3g, h). The gene discussed is IGFBP3; the disease is type 1 diabetes mellitus.