HSPA5 and cancer: For instance, activating transcription factor 4 (ATF4) is a transcription factor that activates HSPA5, which binds to GPX4 to prevent its degradation and subsequently helps cancer cells resist ferroptosis.[105] Under endoplasmic reticulum stress, ATF4 directly and transcriptionally activates ferroptosis-related proteins, such as SLC7A11, HSPA5, and CHOP, to either promote or inhibit ferroptosis.[39] Whether ATF4 and other members of the ATF family simultaneously regulate ferroptosis and immune checkpoints at the transcriptional level warrants further investigation.