Such unusual amino acid compositions may predispose these proteins to misfold and aggregate thereby requiring chaperones to stabilize their conformations. Many exported proteins including knob components contain a penta-peptide export signal known as the PEXEL motif. Recent advances reveal that PEXEL-proteins are transported across the parasitophorous vacuolar LDN-193189 ALK inhibitor membrane through an integral membrane PEXEL translocon. The trafficking of PEXEL containing proteins across this translocon may likely involve protein unfolding and refolding events, thereby requiring involvement of chaperones. There is very little known about the export of knob components and mechanism of their assembly. Trafficking of proteins across membranes typically involves the action of several molecular chaperones, generally of the Hsp40 class. However, specific players in the trafficking of knob components have not been studied. While analyzing the chaperone coding genes of the parasite, we found that of the 18 PEXEL containing Hsp40s, PF3D7_0201800 was present in a cluster with PfEMP3 and KAHRP on the subtelomeric end of chromosome 2. Chromosomal clusters in the parasite are defined on the basis of identical transcription profile within the same developmental stage of the parasite. Parasite knobs are one of the largest and most complex macromolecular assemblies, measuring 100–120 nm on the erythrocyte plasma membrane. Assembly of such a large and heterogeneous structure may necessitate the involvement of specific chaperones owing to their ability to fold, unfold and stabilize proteins. A recent structural study addressed biophysically the question of how PfEMP1-ATS anchors to host cells in order to facilitate knob assembly. Surprisingly, ATS-KAHRP interaction did not seem to be important for this purpose, however, a PHIST-domain containing parasite protein was found to be involved. It further supports our hypothesis of chaperones being involved in knob assembly as many of the exported chaperones also contain PHIST domains. All chaperone proteins that are predicted to be exported belong to the Hsp40 class. This is not very surprising as Hsp40s have been shown to perform a wide variety of functions in other biological systems and therefore could be the major players for host cell remodeling. While observing the genomic location of these Hsp40s, we found that PFB0090c/PF3D7_0201800 lies along side genes encoding knob proteins KAHRP and PfEMP3, forming a cluster at the subtelomeric end of chromosome 2. It was interesting to note that these genes exhibit an overlap in their time of expression showing transcript peaks within the same time window in the asexual blood stages of the parasite. KAHsp40 turned out to be an exported protein by virtue of a PEXEL signal at its Nterminus. We therefore decided to investigate the localization, export and possible interactors of KAHsp40 in the infected erythrocyte in order to gain better insight into its function. In agreement to the presence of a PEXEL motif, we found KAHsp40 being exported out to the erythrocyte cytosol in trophozoite stages, which coincides with the appearance of knobs on the infected erythrocyte surface. IFA analysis indicated that KAHsp40 is exported out of the parasite in discrete foci distinct from Maurer’s cleft at the infected erythrocyte periphery. Stage specific IPs revealed that KAHsp40 remains entirely intra-parasitic up to 8 hours post invasion and is exported only in the trophozoite stages. Indeed, we also found KAHsp40 to co-localize with KAHRP on the infected erythrocyte membrane. KAHRP is known to accumulate only on the cytoplasmic side of knobs.