Our data indicate pivotal therapeutic potential of PIAA, which drives proliferation of β-cells via its TBK1 inhibitory activity with additional pro-differentiation effect, for expanding functional β-cells in physiological (rat and hESC-derived β-cells and isolated non-diabetic human islets) and pathophysiological conditions (cytokine- and glucotoxicity-treated β-cells, STZ-induced diabetic mice, and T2D human islets); under pathophysiological conditions, TBK1 expression was induced. The gene discussed is TBK1; the disease is type 2 diabetes mellitus.