The main goal of NE-CAT is to provide user access to state-of-the-art synchrotron beamlines for macromolecular crystallography. NE-CAT began planning and design for two beamlines in 2001. Beamline 24-ID-C became available to Advanced Photon Source users in 2006 and beamline 24-ID-E became available in 2007. During the ensuing years, beamline improvements have resulted in stable, small X-ray beams ideally suited for challenging problems in macromolecular crystallography. Each beamline is equipped with a high capacity sample automounter and a microdiffractometer. Beamline 24-ID-C features an EIGER2 X 16M pixel array detector, and 24-ID-E features an EIGER X 16M. NE-CAT provides automated software for data collection and analysis (RAPD) and a web-based interface for remote data collection. We will continue to provide routine maintenance to ensure efficient and reliable data collection, and we propose an upgrade program to maintain state-of-the-art capabilities over the five years covered by this application. This period includes 12 months without X-rays required for the APS upgrade project. We will use this superb opportunity to rebuild a nearly 20-year-old system to be leaders in the field for another 20 years. NE-CAT has an experienced and dedicated scientific staff who enable access to the beamlines. The staff is available or on call 24/7 to assist users with data collection and processing needs. This highly regarded staff is a major strength of NE-CAT. NE-CAT has an outstanding record of reliability with technical problems rarely interfering with user access. NE-CAT is directed by Dr. Steven Ealick, who has more that 30 years of experience overseeing the operation of synchrotron facilities for macromolecular crystallography. The technical group, led by Deputy Director Dr. Malcolm Capel, and the operations group, led by Associate Director Dr. Frank Murphy work closely together to ensure that the needs of the user community are met. Together, these three individuals make up the NE-CAT management team. NE-CAT beam time is in high demand, and each run all available beam time is allocated to users. NE-CAT typically hosts more than 1500 users per year from about 160 unique user groups, either on site or remotely. NE- CAT users published about 200 papers during the last year and are projected to publish more than 190 in 2021. NE-CAT’s record of productivity places it among the top of worldwide facilities for macromolecular crystallography. NE-CAT operates an extensive user training program adaptable to first time users, advanced users with technically challenging problems, and everyone in between. A website is available to provide all information needed by new or current users. NE-CAT participates in many training and outreach activities including organization of an annual workshop and participation in professional society meetings. The staff works closely with user groups and are often invited to coauthor manuscripts resulting from user support and tr...