The multifactorial steroid-induced osteonecrosis of the femoral head (SONFH) is known to have a genetic component, but its pathoetiology remains incompletely elucidated.In this issue, Chen et al. (p.2378) report that rare variants in ANK1 and EPB41 are novel SONFH disease risk factors that compromise erythrocyte membrane integrity, exacerbating microcirculatory damage when glucocorticoids serve as a second hit.In eukaryotic cells such as erythrocytes, ankyrin 1 (encoded by ANK1) and membrane protein band 4.1 (encoded by EPB41) connect the plasma membrane with the and mechanical integrity.
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