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Several parasite proteins including Photosensitized INA-labelled protein 1 (PhIL1) have been shown to associate with glideosome machinery. Here we describe a novel PhIL1 associated protein complex that co-exists with the glideosome motor complex in the inner membrane complex of the merozoite. Using an experimental genetics approach, we characterized the role(s) of three proteins associated with PhIL1: a glideosome associated protein- PfGAPM2, an IMC structural protein- PfALV5, and an uncharacterized protein\u2014referred here as PfPhIP (\n                    <jats:underline>Ph<\/jats:underline>\n                    IL1\n                    <jats:underline>I<\/jats:underline>\n                    nteracting\n                    <jats:underline>P<\/jats:underline>\n                    rotein). Parasites lacking PfPhIP or PfGAPM2 were unable to invade host RBCs. Additionally, the downregulation of PfPhIP resulted in significant defects in merozoite segmentation. Furthermore, the PfPhIP and PfGAPM2 depleted parasites showed abrogation of reorientation\/gliding. However, initial attachment with host RBCs was not affected in these parasites. Together, the data presented here show that proteins of the PhIL1-associated complex play an important role in the orientation of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    merozoites following initial attachment, which is crucial for the formation of a tight junction and hence invasion of host erythrocytes.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009750","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T14:24:04Z","timestamp":1627568644000},"page":"e1009750","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Plasmodium falciparum PhIL1-associated complex plays an essential role in merozoite reorientation and invasion of host erythrocytes"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-6108","authenticated-orcid":true,"given":"Ekta","family":"Saini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-3398","authenticated-orcid":true,"given":"Pradeep Kumar","family":"Sheokand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2133-3704","authenticated-orcid":true,"given":"Vaibhav","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3641-4814","authenticated-orcid":true,"given":"Prakhar","family":"Agrawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderjeet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-6605","authenticated-orcid":true,"given":"Shailja","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-1979","authenticated-orcid":true,"given":"Asif","family":"Mohmmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7384-6280","authenticated-orcid":true,"given":"Pawan","family":"Malhotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"issue":"6","key":"ppat.1009750.ref001","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1083\/jcb.201206112","article-title":"The 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