Orphan proteins and the HSR. (A) Accumulation of oRPs, oMPs, and oTAPs titrate the chaperone Hsp70 and its coregulator, the J-domain protein Sis1, away from Hsf1, activating the HSR. (B) Variation in the activity of the HSR, global protein synthesis, and the putative accumulation of orphan proteins as a function of temperature, highlighting key temperatures associated with growth, HSR maximal activity, condensation of different SG components, and cell death.