Transmembrane proteins represent almost one third of the total cellular proteome, and the majority of them requires translocation into the endoplasmic reticulum (ER) to be folded, sorted and transported to their final subcellular destination. High translational rates during exponential cell growth result in a massive influx of immature proteins into the ER, requiring rapid and accurate folding. Upon proteostatic stress, sensed by the unfolded protein response (UPR), cells increase their ER folding capacity via upregulation of chaperones, folding enzymes and lipid synthesis enzymes to expand the ER membrane. Moreover, different branches of the ER-associated degradation (ERAD) pathway detect and degrade misfolded proteins to prevent protein aggregation in the ER. In this thesis, we identified Snd3 as a novel ER transmembrane chaperone in yeast that is required for the stability of a subset of integral ER proteins, affecting membrane contact site formation and lipid homeostasis. Formation and expansion of the nucleus-vacuole junctions (NVJs), which establish close proximity between the perinuclear ER and the vacuole, not only depended on the presence of Snd3 but also contributed to its spatial organisation within the cell. This chaperone was essential for the stability of the main NVJ tethering protein Nvj1 and in addition concentrated at the NVJs upon glucose exhaustion. Glucose re-addition triggered its rapid disassociation from the NVJs, linking cellular metabolism with membrane contact site dynamics (paper I). Fluorescence and electron microscopy combined with proteomics of microsomal fractions and aggregate isolation revealed the importance of Snd3 for the folding and stability of a subset of ER transmembrane proteins besides Nvj1, with severe effects on the cellular lipidome (paper II). Both functional UPR and ERAD were essential for cell viability upon loss of Snd3. In addition, ER membrane expansion to cope with proteostatic stress was compromised in absence of Snd3, which was due to defective retention of the transcriptional repressor Opi1 at the perinuclear ER, resulting in excess nuclear translocation of Opi1 and insufficient expression of genes required for phospholipid synthesis (paper II). Lipidomic analyses not only revealed a decrease of phosphatidic acid, the phospholipid necessary to anchor Opi1 to the ER membrane, but also an accumulation of very long chain fatty acids (VLCFAs), resulting in overproduction of sphingolipids. Limiting VLCFA synthesis by genetic inactivation of the elongase Elo2 restored contact site formation via stabilisation of Nvj1 and prevented premature cell death (paper III). In sum, we identified a novel molecular chaperone that is required for proper folding of a subset of ER transmembrane proteins, including Nvj1, and thus is critical for efficient membrane contact site formation. When cells exit cell cycle and enter stationary phase due to glucose exhaustion, Snd3 is recruited to the NVJs, where it is stored until glucose availability supports regrowth and the need for folding capacity within the ER increases. Thus, protein targeting to the NVJs contributes to the coordination of cellular folding capacity and lipid metabolism in response to metabolic cues.