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GnRH activates the unfolded protein response (UPR). GnRH activates two of the three known endoplasmic reticulum (ER)-resident stress sensors, ERN1 and EIF2AK3 through calcium mobilization. ERN1 regulates splicing of the mRNA for XBP1, a transcription factor for genes involved in the degradation of misfolded proteins. EIF2AK3 phosphorylates translation initiation factor EIF2A, causing a transient attenuation of translation of select mRNAs such as that encoding luteinizing hormone, a key regulator of ovulation. Therefore, the multifaceted regulatory action of GnRH now includes the UPR, thereby affecting quality control of protein folding within the ER. From the article by Do et al., in this issue, pages 100–112.