Sometimes, size does matter.

It does in the case of a donation from the Helen Diller  Foundation to UCSF announced this week. At $500 million, it is the largest single gift the foundation has granted, and the largest UCSF has received.

The university, which specializes in the medical fields, will deposit $400 million of the gift into its $2.25 billion endowment, bolstering it by 18 percent. The final $100 million will be used to launch an innovation fund to further research and other UCSF projects.

The Diller gift is one of the largest ever given to a public university, rivaled only by a similarly sized 2016 pledge from Nike founder Phil Knight to the University of Oregon. However, the Diller funds are largely unrestricted, meaning they may be applied as UCSF decision-makers see fit.

Sue Cunningham, CEO of the Council for Advancement and Support of Education, which monitors and supports philanthropy to higher education, described the Diller gift as “one of the most significant gifts made to any university in the world. The impact on the long term is truly profound.”

She emphasized the unusual nature of an unrestricted gift of this size, noting that recent data show that only 6.7 percent of all philanthropy to higher education last year came in the form of unrestricted funds.

“Other philanthropists will look at this and will be inspired to think about doing something in the space they are passionate about,” said the Washington, D.C.-based CEO.

San Francisco native Helen Diller began planning the gift in the months before she died in January 2015.

“There was a belief the institution could impact health care worldwide in a big way,” said her daughter, Jackie Safier, who serves as president of the family foundation board. “She wanted to take this opportunity to do something world-changing.”

UCSF is home to a three-campus medical center, the UCSF Benioff Children’s Hospitals and professional schools in medicine, dentistry, nursing and pharmacy. There are more than 3,000 faculty members, 22,000 staffers and 3,300 students at the schools.

The Diller gift is one of the largest ever given to a public university.

Helen Diller and the Diller Foundation are well-known in the Bay Area Jewish community. Thousands of teens have participated in the Diller Teen Fellowship, drawing them closer to Israel and Jewish peoplehood. The Diller Teen Tikkun Olam Awards have granted thousands of dollars to innovative Bay Area Jewish teens, while the Diller Family Award for Excellence in Jewish Education annually rewards standout Bay Area Jewish educators.

The late philanthropist, who was born in Mount Zion Hospital (now a UCSF facility), had a soft spot in her heart for UCSF.

In 2003, the foundation donated $35 million to establish the UCSF Helen Diller Family Comprehensive Cancer Center at the university’s Mission Bay campus. Including the just-announced gift, the Diller family has given $650 million to the institution.

“My mother and our whole family have been in awe of the brilliant minds at UCSF,” Safier said. “It’s a place for the best and brightest. These are folks literally changing the face of health care.”

UCSF Chancellor Sam Hawgood calls the half-billion-dollar gift “transformative,” noting that now more endowment proceeds may be devoted to recruiting top students and faculty for UCSF schools.

“We’re only as good as the people we attract,” Hawgood said. “They are the ones who change society for the better. [The gift] enables me to provide additional security to faculty, to secure faculty from all around the world, to take on the high-risk questions faculty want to do. When they succeed, it will change society.”

He also said that the funds, some of which may be used to offset tuition and other costs, would give UCSF students financial security. “They will get the kind of support they need,” Hawgood said, “so at the time of graduation they will not be crippled with debt.”

As for the innovation fund, it will allow Hawgood and future UCSF chancellors to fund promising research and other urgent needs.

“These incredibly precious dollars allow me to react quickly to rapidly moving science,” he added. “I have faculty coming in my office every day with potentially world-changing ideas. This fund gives me the resources to unleash the passion and power of our faculty in ways we have not had before.”

Safier, who runs the family business, Prometheus Real Estate Group, and who also sits on the UCSF Foundation board of overseers, views the $500 million gift as a natural extension of her late mother’s generosity.

“I won the lottery in mothers,” she said. “She was an incredibly optimistic, positive person to her core. She was really appreciative, and never dreamed she could do this much.”