Cell-to-cell communication in plants includes the selective trafficking of transcription factors and other signals through plasmodesmata. The KNOTTED1 (KN1) homeobox (KNOX) family transcription factors, which use this pathway, are essential for stem cell establishment and/or maintenance. Here we show that KN1 trafficking requires the chaperonin complex, which belongs to a group of cytosolic chaperones that fold specific substrate proteins. Genetic and physical interaction data show a functional relevance for chaperonins in KNOX family-dependent stem cell maintenance. Furthermore, tissue-specific complementation assays indicate a mechanistic basis for chaperonin function during the posttranslocational refolding process. Our study shows that chaperonins are essential for the cell-to-cell trafficking of a subset of mobile transcription factors and demonstrates the importance of chaperonin-dependent protein trafficking for plant stem cell function.