While TTR reduction may also cause neural-specific hypothyroidism whereby prenatal and postnatal brain development can be stunted [59], our data from TTR and LRPAP treatment in NGLY1-deficient CO cells exposed to bortezomib (Fig. 6A, B) indicated that TTR downregulation due to NGLY1 malfunction could impair LRP2-mediated neuroprotection and subsequently affect stress tolerability in developing neural cells. This evidence concerns the gene TTR and hypothyroidism.