ATF4 and keratoconus: ISR is initiated through phosphorylation at Ser 51 and activation of the translation elongation initiation factor subunit α (eIF2α) which down regulates protein synthesis to conserve energy20, but upregulates activating transcription factor (ATF4) mediating transcriptional programs underlying metabolism, autophagy and cell survival.19,35,36 We tested if KC cells, even without a serum-starvation challenge, have elevated p-eIF2α.